The present disclosure relates to an implantable drug delivery system for the treatment of erectile dysfunction.
Erectile dysfunction (“ED”), sometimes called impotence, is the repeated inability to achieve or maintain an erection firm enough for sexual intercourse. The word impotence may also be used to describe other problems that interfere with sexual intercourse and reproduction, such as lack of sexual desire and problems with ejaculation or orgasm. ED can be a total inability to achieve erection, an inconsistent ability to do so, or a tendency to sustain only brief erections. In older men, ED usually has a physical cause, such as disease, injury, or side effects of drugs. Any disorder that causes injury to the nerves or impairs blood flow in the penis has the potential to cause ED. ED is treatable at any age, and awareness of this fact has been growing.
The penis contains two chambers called the corpora cavernosa, which run the length of the organ. A spongy tissue fills the chambers. The corpora cavernosa are surrounded by a membrane, called the tunica albuginea. The spongy tissue contains smooth muscles, fibrous tissues, spaces, veins, and arteries. The urethra, which is the channel for urine and ejaculate, runs along the underside of the corpora cavernosa and is surrounded by the corpus spongiosum. Erection begins with sensory or mental stimulation, or both. Impulses from the brain and local nerves cause the muscles of the corpora cavernosa to relax, allowing blood to flow in and fill the spaces. The blood creates pressure in the corpora cavernosa, making the penis expand. The tunica albuginea helps trap the blood in the corpora cavernosa, thereby sustaining erection. When muscles in the penis contract to stop the inflow of blood and open outflow channels, erection is reversed.
Current drugs for treating ED can be taken orally, injected directly into the penis, or inserted into the urethra at the tip of the penis. In 1998 the Food and Drug Administration approved sildenafil citrate (Viagra®, Pfizer, Inc.), the first pill to treat ED. Since that time, vardenafil HCl (Levitra®, Bayer Healthcare Pharmaceuticals, Inc.) and tadalafil (Cialis®, Eli Lilly & Co.) have also been approved. Additional oral medicines are being tested for safety and effectiveness. These drugs work by affecting certain parts of the signal pathway involved with penile smooth muscle relaxation, thus forcing smooth muscle relaxation and increasing the likelihood of achieving an erection.
Sildenafil citrate, vardenafil HCl, and tadalafil all belong to a class of drugs called phosphodiesterase (PDE) inhibitors. Taken an hour before sexual activity, these drugs enhance the effects of nitric oxide, a chemical that relaxes smooth muscles in the penis during sexual stimulation and allows increased blood flow. While oral medicines improve the response to sexual stimulation, they do not trigger an automatic erection, as injections do. Men who take nitrate-based drugs such as nitroglycerin for heart problems should not use PDEs because the combination can cause a sudden drop in blood pressure. Furthermore, taking a PDE inhibitor and an alpha-blocker, used to treat prostate enlargement or high blood pressure, at the same time can cause a sudden drop in blood pressure. And while these drugs are often effective in triggering the onset of an erection, they do not provide an immediate response to sexual stimulation. Additionally, drugs that are ingested orally require a total dose much larger than the minimal amount needed to stimulate the target site, resulting in side effects such as headache, facial flushing, upset stomach and sudden loss of vision. By utilizing a local drug delivery system, higher concentrations could be achieved at the target site even with the use of smaller dosages.
Oral testosterone can reduce ED in some men with low levels of natural testosterone, but it is often ineffective and may cause liver damage. Patients also have claimed that other oral drugs—including yohimbine hydrochloride, dopamine and serotonin agonists, and trazodone—are effective, but the results of scientific studies to substantiate these claims have been inconsistent.
Many men may achieve stronger erections by injecting drugs into the penis, causing it to become engorged with blood. Drugs such as prostaglandin E1, papaverine HCl, phentolamine, and alprostadil (Caverject®, Pfizer, Inc.) have been used for this purpose. For example, alprostadil induces erection by relaxation of trabecular smooth muscle and by dilation of cavernosal arteries. This leads to expansion of lacunar spaces and entrapment of blood by compressing the venules against the tunica albuginea, a process referred to as the corporal veno-occlusive mechanism. A major drawback of these therapies is that a patient must inject these drugs directly into the penis immediately prior to sexual intercourse, in addition, repeated administration may result in scarring.
A system for inserting a pellet of alprostadil into the urethra is marketed as Muse® (Vivus, Inc.). The system uses a pre-filled applicator to deliver the pellet about an inch deep into the urethra. An erection will begin within 8 to 10 minutes and may last 30 to 60 minutes. Common side effects are aching in the penis, testicles, and area between the penis and rectum; warmth or burning sensation in the urethra; redness from increased blood flow to the penis; and minor urethral bleeding or spotting. Like the injection therapies, a major drawback is that the application of the pellet must take place immediately prior to sexual intercourse.
External mechanical vacuum devices may be used to cause an erection by creating a partial vacuum, drawing blood into the penis, engorging and expanding it. These devices are typically only marginally effective and their use can cause embarrassment to the patient.
Surgery is sometimes employed as a treatment for ED, and usually has one of three goals: to implant a prostheses; to reconstruct arteries to increase flow of blood to the penis; or to block off veins that allow blood to leak from the penile tissues.
Mechanical prosthetic implants can simulate an erection in many men with ED. Several designs are currently employed, including one design that uses balloon-like chambers implanted within the penis, a small fluid reservoir implanted within the body and a manual pump mechanism implanted in the scrotum, which drives fluid from the reservoir to the chambers, thereby simulating an erection. Malleable implants usually consist of paired rods, which are inserted surgically into the corpora cavernosa. The user manually adjusts the position of the penis and, therefore, the rods. Adjustment does not affect the width or length of the penis. Drawbacks of implants include mechanical breakdown and infection, the need for fairly invasive surgery, damage to previously-intact penile tissue, and the fact that the erection achieved is not physiologically natural, i.e., not caused by blood pressure and blood volume changes within the penile tissues, resulting in a hindered sexual experience.
Surgery to repair arteries can reduce ED caused by obstructions that block the flow of blood. The best candidates for such surgery are young men presenting with discrete blockage of an artery, usually due to an injury to the crotch or fracture of the pelvis. The procedure is almost never successful in older men with widespread blockage. Surgery to veins that allow blood to leave the penis usually involves an opposite procedure—intentional blockage. Blocking off veins (ligation) can reduce the leakage of blood that diminishes the rigidity of the penis during erection. However, experts have raised questions about the long-term effectiveness of this procedure, and it is rarely performed.
Each of these methods treat ED to varying degrees, but each has their drawbacks such as systemic side effects, poor response times, cumbersome or painful delivery mechanisms, need for traumatic surgery and physiologically unnatural results. In addition, many of these methods are unable to achieve a physiologically natural erection and all require at least some amount of, and sometimes significant, pre-intercourse intervention.